Lab Projects

Fetal Therapy for Krabbe Disease

Krabbe (crab-ā) disease is a fatal lysosomal storage disorder resulting from a mutation in the glucocerebrosidase gene. Without a functional gene, patients have accumulation of a byproduct called psychosine that is toxic to the cells in the brain and peripheral nervous system that produces the myelin required for the transduction of neuronal signals. With progressive neurodegeneration of infantile-onset Krabbe, patients often die by the age of 2. The only therapy for infantile-onset Krabbe disease is a hematopoietic stem cell transplant, however this can only be given prior to symptom onset and even then has high morbidity and poor outcomes. Given the devastating outcomes of this disease, it is ideal for the study of prenatal intervention.

Current FDA-approved gene therapies all utilize adeno-associated viral (AAV) gene delivery given the low immune response and minimal off-target integration. For rapid translation to the clinical setting, AAV vectors have the most direct path forward. Certain AAV serotypes including AAV9 can even cross the neonatal blood brain barrier. We are investigating the prenatal delivery of AAV vectors to treat Krabbe disease before birth.

Bringing Clinical Trials for Fetal Gene and Cell Therapies to Cincinnati Children’s

As new gene and cellular therapies emerge for fetal treatment, Cincinnati Children’s is uniquely poised to coordinate with clinical trials. The Cincinnati Children’s Fetal Care Center is one of the highest volume centers in the country. As a quaternary center, Cincinnati Children’s cares for many rare single gene disorders that may benefit from gene and cellular therapy. Plus, the Division of Human Genetics has a clinical trial program with vast experience coordinating industry and academic trials.